The need for precisely analyzing nanometer-sized particles (referred to as “nanoparticles” and including particles from about 1 nm to 1000 nm) is growing rapidly, as technology is trending towards minimizing the size of electronics and medical science is pushing diagnostics to the limit of recognizing individual biological molecules. A quantitative size/mass spectrometer that can work in solution, and work at single nanoparticle sensitivity, would allow for adding important information to body fluid analysis. Label-free sensors with this capability could identify viruses and exosomes not only by using bound antibodies, but also through their size. Furthermore, monitoring water resources for contamination with harmful nanoparticles, a waste product of the new technologies, is also an emerging need.
The sensitivity of whispering gallery mode (“WGM”) resonances (referred to simply as “WGMs”) of a WGM resonator to changes in its external environment has established WGM resonators as a leading platform for sensitive detection. (See, e.g., X. D. Fan, I. M. White, S. I. Shopova, H. Y. Zhu, J. D. Suter, and Y. Z. Sun, Anal, Chim. Acta 620, 8 (2008) (incorporated herein by reference).) Previous work by one of the present inventors pioneered a mechanism for detection based on WGMs. (See, e.g., S. Arnold, I. Teraoka, U.S. Pat. No. 7,491,491, “Detecting and/or Measuring a Substance Based On a Resonance Shift of Photons Orbiting Within a Microsphere” (incorporated herein by reference),) Plasmonic enhancement brought the sensitivity of a hybrid WGM-local surface plasmon resonator to the realm of detecting single nanoparticles/biomolecules. (See, e.g., S. Shopova, S. Arnold, R. Rajmangal, U.S. Pat. No. 8,493,560, 2013 “Plasmonic Enhancement of Whispering Gallery Mode Biosensors” (incorporated herein by reference).)
The present inventors were able to estimate the size of a particles adsorbed on a WGM resonator based on the largest change in the resonant frequency in a distribution of many events. However, such statistical techniques are non-deterministic and require many event samples.
U. S. Patent Application Publication No. 2010/0085573 (incorporated herein by reference), titled “Split Frequency Sensing Methods and Systems” discusses resonant sensors and molecule detection methods utilizing split frequency, but has some limitations, and is not used for determining the size (e.g., volume) and/or mass of a nanoparticle.